9-128343291-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005094.4(SLC27A4):c.159C>T(p.Ile53=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC27A4 NM_005094.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.001547
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.432

Genes affected

SLC27A4 (HGNC:10998): (solute carrier family 27 member 4) This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-128343291-C-T is Benign according to our data. Variant chr9-128343291-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2797640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.432 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC27A4	NM_005094.4	c.159C>T	p.Ile53=	splice_region_variant, synonymous_variant	2/13	ENST00000300456.5
SLC27A4	XM_047422664.1	c.192C>T	p.Ile64=	splice_region_variant, synonymous_variant	2/13
SLC27A4	XM_017014222.2	c.159C>T	p.Ile53=	splice_region_variant, synonymous_variant	3/14
SLC27A4	XM_024447391.2	c.159C>T	p.Ile53=	splice_region_variant, synonymous_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A4	ENST00000300456.5	c.159C>T	p.Ile53=	splice_region_variant, synonymous_variant	2/13	1	NM_005094.4	P1
SLC27A4	ENST00000372870.5	c.231+10C>T		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	10
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131105570;